Bioprosthetic heart valves are now used in an estimated 200,000 patients annually world wide. They generally fail over time due to heterograft leaflet malfunction. In about 80% of cases, bioprosthetic leaflet calcification is the cause of failure, and there has been an extensive amount of research related to this failure mechanism. The remaining 20% of these bioprostheses fail without evidence of calcification. Efforts have been made to prevent degeneration of bioprosthetic heart valves by mitigating calcification.
Oxidative stress occurs in living organisms due to an inflammatory cell response that gives rise to reactive oxygen species (ROS), and these can include nitric oxide, peroxynitrite, hydrogen peroxide, and superoxides. ROS can modify proteins and other macromolecules with either loss of function or structural damage. Living cells maintain an anti-oxidant system involving chiefly intracellular glutathione, and a variety of enzymes that can break down ROS. These ROS-enzymes include superoxide dismutase, catalase, glutathione reductase and others.
It has been reported that hypertension and metabolic disorders are two common risk factors for degenerative aortic valve disease (DAVD) (Yehgiazaryan et al. Infectious Disorders—Drug Targets 2008; 8:88-99). Metabolic syndrome (MS) has been found associated independently with accelerated degeneration of bioprosthetic valves (Briand et al. Circulation 2006; 114:I-512-7). However, whether oxidative stress is a contributing cause of the material failure of bioprosthetic heart valves has not been studied. Nor has the possibility of using anti-oxidants for preventing bioprosthetic heart valve leaflet deterioration been considered or reported.
Therefore, there remains a need for an effective treatment for preventing degeneration of bioprosthetic tissues in a subject.